Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and...Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular level.However,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to date.Here,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular nanomedicines.Poly(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in macrophages.By adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with nanoparticles.Nano-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over time.Based on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation timelines.More importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in cells.In summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.展开更多
Non-descriptive and convenient labels are uninformative and unfairly project blame onto patients.The language clinicians use in the Electronic Medical Record,research,and clinical settings shapes biases and subsequent...Non-descriptive and convenient labels are uninformative and unfairly project blame onto patients.The language clinicians use in the Electronic Medical Record,research,and clinical settings shapes biases and subsequent behaviors of all providers involved in the enterprise of transplantation.Terminology such as noncompliant and nonadherent serve as a reason for waitlist inactivation and limit access to life-saving transplantation.These labels fail to capture all the circum-stances surrounding a patient’s inability to follow their care regimen,trivialize social determinants of health variables,and bring unsubstantiated subjectivity into decisions regarding organ allocation.Furthermore,insufficient Medicare coverage has forced patients to ration or stop taking medication,leading to allograft failure and their subsequent diagnosis of noncompliant.We argue that perpetuating non-descriptive language adds little substantive information,in-creases subjectivity to the organ allocation process,and plays a major role in reduced access to transplantation.For patients with existing barriers to care,such as racial/ethnic minorities,these effects may be even more drastic.Transplant committees must ensure thorough documentation to correctly encapsulate the entirety of a patient’s position and give voice to an already vulnerable population.展开更多
BACKGROUND Panic disorder(PD)involves emotion dysregulation,but its underlying mechanisms remain poorly understood.Previous research suggests that implicit emotion regulation may play a central role in PD-related emot...BACKGROUND Panic disorder(PD)involves emotion dysregulation,but its underlying mechanisms remain poorly understood.Previous research suggests that implicit emotion regulation may play a central role in PD-related emotion dysregulation and symptom maintenance.However,there is a lack of studies exploring the neural mechanisms of implicit emotion regulation in PD using neurophysiological indicators.AIM To study the neural mechanisms of implicit emotion regulation in PD with eventrelated potentials(ERP).METHODS A total of 25 PD patients and 20 healthy controls(HC)underwent clinical evaluations.The study utilized a case-control design with random sampling,selecting participants for the case group from March to December 2018.Participants performed an affect labeling task,using affect labeling as the experimental condition and gender labeling as the control condition.ERP and behavioral data were recorded to compare the late positive potential(LPP)within and between the groups.RESULTS Both PD and HC groups showed longer reaction times and decreased accuracy under the affect labeling.In the HC group,late LPP amplitudes exhibited a dynamic pattern of initial increase followed by decrease.Importantly,a significant group×condition interaction effect was observed.Simple effect analysis revealed a reduction in the differences of late LPP amplitudes between the affect labeling and gender labeling conditions in the PD group compared to the HC group.Furthermore,among PD patients under the affect labeling,the late LPP was negatively correlated with disease severity,symptom frequency,and intensity.CONCLUSION PD patients demonstrate abnormalities in implicit emotion regulation,hampering their ability to mobilize cognitive resources for downregulating negative emotions.The late LPP amplitude in response to affect labeling may serve as a potentially valuable clinical indicator of PD severity.展开更多
The halopyrimidine 5-bromo-2′-deoxyuridine(BrdU)is an exogenous marker of DNA synthesis.Since the introduction of monoclonal antibodies against BrdU,an increasing number of methodologies have been used for the immuno...The halopyrimidine 5-bromo-2′-deoxyuridine(BrdU)is an exogenous marker of DNA synthesis.Since the introduction of monoclonal antibodies against BrdU,an increasing number of methodologies have been used for the immunodetection of this synthesized bromine-tagged base analogue into replicating DNA.BrdU labeling is widely used for identifying neuron precursors and following their fate during the embryonic,perinatal,and adult neurogenesis in a variety of vertebrate species including birds,reptiles,and mammals.Due to BrdU toxicity,its incorporation into replicating DNA presents adverse consequences on the generation,survival,and settled patterns of cells.This may lead to false results and misinterpretation in the identification of proliferative neuroblasts.In this review,I will indicate the detrimental effects of this nucleoside during the development of the central nervous system,as well as the reliability of BrdU labeling to detect proliferating neuroblasts.Moreover,it will show factors influencing BrdU immunodetection and the contribution of this nucleoside to the study of prenatal,perinatal,and adult neurogenesis.Human adult neurogenesis will also be discussed.It is my hope that this review serves as a reference for those researchers who focused on detecting cells that are in the synthetic phase of the cell cycle.展开更多
Small peptides have attracted increasing attention for their unique features and diverse biological functions.Achieving rapid separation and accurate quantification,however,remains a challenge because of their low abu...Small peptides have attracted increasing attention for their unique features and diverse biological functions.Achieving rapid separation and accurate quantification,however,remains a challenge because of their low abundance and the co-existence of numerous structural isomers.In this study,we developed a novel approach using isotope chemical labeling for ultrasensitive determination of di/tripeptides in biological samples.We successfully synthesized a novel derivatization reagent,4-(2-(ethoxymethylene)-3-oxobutanamido)-N,N,N-trimethylbenzenaminium iodide(EOTMBA)as well as its deuterium-labeled isotope reagent(d_(3)-EOTMBA).A total of 97 small peptides,including 89 dipeptides and 8 tripeptides,could be completely derivatized in methanol within 1.5h at 60℃.After EOTMBA labeling,analysis of these di/tripeptides were achieved within 22 min by LC-MS/MS analysis.The method demonstrated 86.3%-113%accuracy and the limit of quantification ranged from 0.25 fmol/L to 5 nmol/L.Using this method,we achieved ultrasensitive and accurate quantification of di/tripeptides in 147 plasma,49 urine and 46 bile samples obtained from healthy individuals and patients with biliary tract diseases.The identified differential di/tripeptide biomarker panels showed promising diagnostic performance for patients with biliary tract cancer with area under the receiver operating curve values from 0.870 to 0.996.Furthermore,this method was successfully applied to quantify di/tripeptides in the extract of an animal-derived traditional Chinese medicine,Eupolyphaga sinensis Walker.These findings highlight the possible application of the analytical method in clinics and for the purposes of quality control of traditional Chinese medicines.展开更多
BACKGROUND Global and regional cerebral blood flow(CBF)changes in patients with unilateral internal carotid artery occlusion(ICAO)are unclear when the dual post-labeling delays(PLD)arterial spin labeling(ASL)magnetic ...BACKGROUND Global and regional cerebral blood flow(CBF)changes in patients with unilateral internal carotid artery occlusion(ICAO)are unclear when the dual post-labeling delays(PLD)arterial spin labeling(ASL)magnetic resonance imaging(MRI)technique is used.Manual delineation of regions of interest for CBF measurement is time-consuming and laborious.AIM To assess global and regional CBF changes in patients with unilateral ICAO with the ASL-MRI perfusion technique.METHODS Twenty hospitalized patients with ICAO and sex-and age-matched controls were included in the study.Regional CBF was measured by Dr.Brain's ASL software.The present study evaluated differences in global,middle cerebral artery(MCA)territory,anterior cerebral artery territory,and Alberta Stroke Program Early Computed Tomography Score(ASPECTS)regions(including the caudate nucleus,lentiform nucleus,insula ribbon,internal capsule,and M1-M6)and brain lobes(including frontal,parietal,temporal,and insular lobes)between ICAO patients and controls at PLD 1.5 s and PLD 2.5 s.RESULTS When comparing CBF between ICAO patients and controls,the global CBF in ICAO patients was lower at both PLD 1.5 s and PLD 2.5 s;the CBF on the occluded side was lower in 15 brain regions at PLD 1.5 s,and it was lower in 9 brain regions at PLD 2.5 s;the CBF in the contralateral hemisphere was lower in the caudate nucleus and internal capsule at PLD 1.5 s and in M6 at PLD 2.5 s.The global CBF in ICAO patients was lower at PLD 1.5 s than at PLD 2.5 s.The ipsilateral CBF at PLD 1.5 s was lower than that at PLD 2.5 s in 15 regions,whereas the contralateral CBF was lower at PLD 1.5 s than at PLD 2.5 s in 12 regions.The ipsilateral CBF was lower than the contralateral CBF in 15 regions at PLD 1.5 s,and in M6 at PLD 2.5 s.CONCLUSION Unilateral ICAO results in hypoperfusion in the global and MCA territories,especially in the ASPECTS area.Dual PLD settings prove more suitable for accurate CBF quantification in ICAO.展开更多
Recent advances in utilizing ^(17)O isotopic labeling methods for solid-state nuclear magnetic resonance(NMR)investigations of metal oxides for lithium-ion batteries have yielded extensive insights into their structur...Recent advances in utilizing ^(17)O isotopic labeling methods for solid-state nuclear magnetic resonance(NMR)investigations of metal oxides for lithium-ion batteries have yielded extensive insights into their structural and dynamic details.Herein,we commence with a brief introduction to recent research on lithium-ion battery oxide materials studied using ^(17)O solid-state NMR spectroscopy.Then we delve into a review of ^(17)O isotopic labeling methods for tagging oxygen sites in both the bulk and surfaces of metal oxides.At last,the unresolved problems and the future research directions for advancing the ^(17)O labeling technique are discussed.展开更多
The study of the neuron has always been a fundamental aspect when it came to studying mental illnesses such as autism and depression. The protein protocadherin-9 (PCDH9) is an important transmembrane protein in the de...The study of the neuron has always been a fundamental aspect when it came to studying mental illnesses such as autism and depression. The protein protocadherin-9 (PCDH9) is an important transmembrane protein in the development of the neuron synapse. Hence, research on its protein interactome is key to understanding its functionality and specific properties. A newly discovered biotin ligase, TurboID, is a proximity labeler that is designed to be able to label and observe transmembrane proteins, something that previous methods struggled with. The TurboID method is verified in HEK293T cells and primary cultured mouse cortical neurons. Results have proven the validity of the TurboID method in observing PCDH9-interacting proteins.展开更多
Analyzing the structure and function of the brain's neural network is critical for identifying the working principles of the brain and the mechanisms of brain diseases.Recombinant rabies viral vectors allow for th...Analyzing the structure and function of the brain's neural network is critical for identifying the working principles of the brain and the mechanisms of brain diseases.Recombinant rabies viral vectors allow for the retrograde labeling of projection neurons and cell type-specific trans-monosynaptic tracing,making these vectors powerful candidates for the dissection of synaptic inputs.Although several attenuated rabies viral vectors have been developed,their application in studies of functional networks is hindered by the long preparation cycle and low yield of these vectors.To overcome these limitations,we developed an improved production system for the rapid rescue and preparation of a high-titer CVS-N2c-ΔG virus.Our results showed that the new CVS-N2c-ΔG-based toolkit performed remarkably:(1)N2cG-coated CVS-N2c-ΔG allowed for efficient retrograde access to projection neurons that were unaddressed by rAAV9-Retro,and the efficiency was six times higher than that of rAAV9-Retro;(2)the trans-monosynaptic efficiency of oG-mediated CVS-N2c-ΔG was 2–3 times higher than that of oG-mediated SAD-B19-ΔG;(3)CVS-N2c-ΔG could delivery modified genes for neural activity monitoring,and the time window during which this was maintained was 3 weeks;and(4)CVS-N2c-ΔG could express sufficient recombinases for efficient transgene recombination.These findings demonstrate that new CVS-N2c-ΔG-based toolkit may serve as a versatile tool for structural and functional studies of neural circuits.展开更多
The success of deep transfer learning in fault diagnosis is attributed to the collection of high-quality labeled data from the source domain.However,in engineering scenarios,achieving such high-quality label annotatio...The success of deep transfer learning in fault diagnosis is attributed to the collection of high-quality labeled data from the source domain.However,in engineering scenarios,achieving such high-quality label annotation is difficult and expensive.The incorrect label annotation produces two negative effects:1)the complex decision boundary of diagnosis models lowers the generalization performance on the target domain,and2)the distribution of target domain samples becomes misaligned with the false-labeled samples.To overcome these negative effects,this article proposes a solution called the label recovery and trajectory designable network(LRTDN).LRTDN consists of three parts.First,a residual network with dual classifiers is to learn features from cross-domain samples.Second,an annotation check module is constructed to generate a label anomaly indicator that could modify the abnormal labels of false-labeled samples in the source domain.With the training of relabeled samples,the complexity of diagnosis model is reduced via semi-supervised learning.Third,the adaptation trajectories are designed for sample distributions across domains.This ensures that the target domain samples are only adapted with the pure-labeled samples.The LRTDN is verified by two case studies,in which the diagnosis knowledge of bearings is transferred across different working conditions as well as different yet related machines.The results show that LRTDN offers a high diagnosis accuracy even in the presence of incorrect annotation.展开更多
Background In this work,we focus on the label layout problem:specifying the positions of overlaid virtual annotations in Virtual/Augmented Reality scenarios.Methods Designing a layout of labels that does not violate d...Background In this work,we focus on the label layout problem:specifying the positions of overlaid virtual annotations in Virtual/Augmented Reality scenarios.Methods Designing a layout of labels that does not violate domain-specific design requirements,while at the same time satisfying aesthetic and functional principles of good design,can be a daunting task even for skilled visual designers.Presenting the annotations in 3D object space instead of projection space,allows for the preservation of spatial and depth cues.This results in stable layouts in dynamic environments,since the annotations are anchored in 3D space.Results In this paper we make two major contributions.First,we propose a technique for managing the layout and rendering of annotations in Virtual/Augmented Reality scenarios by manipulating the annotations directly in 3D space.For this,we make use of Artificial Potential Fields and use 3D geometric constraints to adapt them in 3D space.Second,we introduce PartLabeling:an open source platform in the form of a web application that acts as a much-needed generic framework allowing to easily add labeling algorithms and 3D models.This serves as a catalyst for researchers in this field to make their algorithms and implementations publicly available,as well as ensure research reproducibility.The PartLabeling framework relies on a dataset that we generate as a subset of the original PartNet dataset consisting of models suitable for the label management task.The dataset consists of 10003D models with part annotations.展开更多
File labeling techniques have a long history in analyzing the anthological trends in computational linguistics.The situation becomes worse in the case of files downloaded into systems from the Internet.Currently,most ...File labeling techniques have a long history in analyzing the anthological trends in computational linguistics.The situation becomes worse in the case of files downloaded into systems from the Internet.Currently,most users either have to change file names manually or leave a meaningless name of the files,which increases the time to search required files and results in redundancy and duplications of user files.Currently,no significant work is done on automated file labeling during the organization of heterogeneous user files.A few attempts have been made in topic modeling.However,one major drawback of current topic modeling approaches is better results.They rely on specific language types and domain similarity of the data.In this research,machine learning approaches have been employed to analyze and extract the information from heterogeneous corpus.A different file labeling technique has also been used to get the meaningful and`cohesive topic of the files.The results show that the proposed methodology can generate relevant and context-sensitive names for heterogeneous data files and provide additional insight into automated file labeling in operating systems.展开更多
Hiding secret data in digital images is one of the major researchfields in information security.Recently,reversible data hiding in encrypted images has attracted extensive attention due to the emergence of cloud servi...Hiding secret data in digital images is one of the major researchfields in information security.Recently,reversible data hiding in encrypted images has attracted extensive attention due to the emergence of cloud services.This paper proposes a novel reversible data hiding method in encrypted images based on an optimal multi-threshold block labeling technique(OMTBL-RDHEI).In our scheme,the content owner encrypts the cover image with block permutation,pixel permutation,and stream cipher,which preserve the in-block correlation of pixel values.After uploading to the cloud service,the data hider applies the prediction error rearrangement(PER),the optimal threshold selection(OTS),and the multi-threshold labeling(MTL)methods to obtain a compressed version of the encrypted image and embed secret data into the vacated room.The receiver can extract the secret,restore the cover image,or do both according to his/her granted authority.The proposed MTL labels blocks of the encrypted image with a list of threshold values which is optimized with OTS based on the features of the current image.Experimental results show that labeling image blocks with the optimized threshold list can efficiently enlarge the amount of vacated room and thus improve the embedding capacity of an encrypted cover image.Security level of the proposed scheme is analyzed and the embedding capacity is compared with state-of-the-art schemes.Both are concluded with satisfactory performance.展开更多
Multi-label classification is a challenging problem that has attracted significant attention from researchers, particularly in the domain of image and text attribute annotation. However, multi-label datasets are prone...Multi-label classification is a challenging problem that has attracted significant attention from researchers, particularly in the domain of image and text attribute annotation. However, multi-label datasets are prone to serious intra-class and inter-class imbalance problems, which can significantly degrade the classification performance. To address the above issues, we propose the multi-label weighted broad learning system(MLW-BLS) from the perspective of label imbalance weighting and label correlation mining. Further, we propose the multi-label adaptive weighted broad learning system(MLAW-BLS) to adaptively adjust the specific weights and values of labels of MLW-BLS and construct an efficient imbalanced classifier set. Extensive experiments are conducted on various datasets to evaluate the effectiveness of the proposed model, and the results demonstrate its superiority over other advanced approaches.展开更多
The Nutri-Score is a 5-color front-of-pack nutrition label designed to provide consumers with an easily understandable guideline to the healthiness of food products.The impact that the Nutri-Score may have on consumer...The Nutri-Score is a 5-color front-of-pack nutrition label designed to provide consumers with an easily understandable guideline to the healthiness of food products.The impact that the Nutri-Score may have on consumers'choices is unclear since different experimental paradigms have found vastly different effect sizes.In the present study,we have investigated how student participants change a hypothetical personal 1-daydietary plan after a learning phase during which they learn about the Nutri-Scores of the available food items.Participants were instructed to compose a healthy diet plan in order that the question of whether the NutriScore would improve their ability to compose a healthy dietary plan could be investigated,independent of the question of whether they would apply this knowledge in their ordinary lives.We found a substantial(Cohen's d=0.86)positive impact on nutritional quality(as measured by the Nutrient Profiling System score of the Food Standards Agency)and a medium-sized(Cohen's d=0.43)reduction of energy content.Energy content reduction was larger for participants who had initially composed plans with higher energy content.The results suggest that the Nutri-Score has the potential to guide consumers to healthier food choices.It remains unclear,however,whether this potential will be reflected in real-life dietary choices.展开更多
Interpreted the latest cosmetic labeling requirements one by one from the basic principles on labels,content, positions, preceded terms and so on;analyzed the relevant cases, so as to help cosmetic manufacturers and o...Interpreted the latest cosmetic labeling requirements one by one from the basic principles on labels,content, positions, preceded terms and so on;analyzed the relevant cases, so as to help cosmetic manufacturers and operation enterprises to deeply understand the latest requirements on cosmetics labeling after the promulgation of the new regulations.展开更多
Recently,weak supervision has received growing attention in the field of salient object detection due to the convenience of labelling.However,there is a large performance gap between weakly supervised and fully superv...Recently,weak supervision has received growing attention in the field of salient object detection due to the convenience of labelling.However,there is a large performance gap between weakly supervised and fully supervised salient object detectors because the scribble annotation can only provide very limited foreground/background information.Therefore,an intuitive idea is to infer annotations that cover more complete object and background regions for training.To this end,a label inference strategy is proposed based on the assumption that pixels with similar colours and close positions should have consistent labels.Specifically,k-means clustering algorithm was first performed on both colours and coordinates of original annotations,and then assigned the same labels to points having similar colours with colour cluster centres and near coordinate cluster centres.Next,the same annotations for pixels with similar colours within each kernel neighbourhood was set further.Extensive experiments on six benchmarks demonstrate that our method can significantly improve the performance and achieve the state-of-the-art results.展开更多
Purpose:Many science,technology and innovation(STI)resources are attached with several different labels.To assign automatically the resulting labels to an interested instance,many approaches with good performance on t...Purpose:Many science,technology and innovation(STI)resources are attached with several different labels.To assign automatically the resulting labels to an interested instance,many approaches with good performance on the benchmark datasets have been proposed for multi-label classification task in the literature.Furthermore,several open-source tools implementing these approaches have also been developed.However,the characteristics of real-world multi-label patent and publication datasets are not completely in line with those of benchmark ones.Therefore,the main purpose of this paper is to evaluate comprehensively seven multi-label classification methods on real-world datasets.Research limitations:Three real-world datasets differ in the following aspects:statement,data quality,and purposes.Additionally,open-source tools designed for multi-label classification also have intrinsic differences in their approaches for data processing and feature selection,which in turn impacts the performance of a multi-label classification approach.In the near future,we will enhance experimental precision and reinforce the validity of conclusions by employing more rigorous control over variables through introducing expanded parameter settings.Practical implications:The observed Macro F1 and Micro F1 scores on real-world datasets typically fall short of those achieved on benchmark datasets,underscoring the complexity of real-world multi-label classification tasks.Approaches leveraging deep learning techniques offer promising solutions by accommodating the hierarchical relationships and interdependencies among labels.With ongoing enhancements in deep learning algorithms and large-scale models,it is expected that the efficacy of multi-label classification tasks will be significantly improved,reaching a level of practical utility in the foreseeable future.Originality/value:(1)Seven multi-label classification methods are comprehensively compared on three real-world datasets.(2)The TextCNN and TextRCNN models perform better on small-scale datasets with more complex hierarchical structure of labels and more balanced document-label distribution.(3)The MLkNN method works better on the larger-scale dataset with more unbalanced document-label distribution.展开更多
Battery pack capacity estimation under real-world operating conditions is important for battery performance optimization and health management,contributing to the reliability and longevity of batterypowered systems.Ho...Battery pack capacity estimation under real-world operating conditions is important for battery performance optimization and health management,contributing to the reliability and longevity of batterypowered systems.However,complex operating conditions,coupling cell-to-cell inconsistency,and limited labeled data pose great challenges to accurate and robust battery pack capacity estimation.To address these issues,this paper proposes a hierarchical data-driven framework aimed at enhancing the training of machine learning models with fewer labeled data.Unlike traditional data-driven methods that lack interpretability,the hierarchical data-driven framework unveils the“mechanism”of the black box inside the data-driven framework by splitting the final estimation target into cell-level and pack-level intermediate targets.A generalized feature matrix is devised without requiring all cell voltages,significantly reducing the computational cost and memory resources.The generated intermediate target labels and the corresponding features are hierarchically employed to enhance the training of two machine learning models,effectively alleviating the difficulty of learning the relationship from all features due to fewer labeled data and addressing the dilemma of requiring extensive labeled data for accurate estimation.Using only 10%of degradation data,the proposed framework outperforms the state-of-the-art battery pack capacity estimation methods,achieving mean absolute percentage errors of 0.608%,0.601%,and 1.128%for three battery packs whose degradation load profiles represent real-world operating conditions.Its high accuracy,adaptability,and robustness indicate the potential in different application scenarios,which is promising for reducing laborious and expensive aging experiments at the pack level and facilitating the development of battery technology.展开更多
基金supported by Natural Science Foundation of Beijing Municipality(L212013)National Key Research and Development Program of China(No.2022YFA1206104)+2 种基金AI+Health Collaborative Innovation Cultivation Project(Z211100003521002)National Natural Science Foundation of China(81971718,82073786,81872809,U20A20412,81821004)Beijing Natural Science Foundation(7222020).
文摘Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular level.However,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to date.Here,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular nanomedicines.Poly(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in macrophages.By adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with nanoparticles.Nano-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over time.Based on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation timelines.More importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in cells.In summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.
文摘Non-descriptive and convenient labels are uninformative and unfairly project blame onto patients.The language clinicians use in the Electronic Medical Record,research,and clinical settings shapes biases and subsequent behaviors of all providers involved in the enterprise of transplantation.Terminology such as noncompliant and nonadherent serve as a reason for waitlist inactivation and limit access to life-saving transplantation.These labels fail to capture all the circum-stances surrounding a patient’s inability to follow their care regimen,trivialize social determinants of health variables,and bring unsubstantiated subjectivity into decisions regarding organ allocation.Furthermore,insufficient Medicare coverage has forced patients to ration or stop taking medication,leading to allograft failure and their subsequent diagnosis of noncompliant.We argue that perpetuating non-descriptive language adds little substantive information,in-creases subjectivity to the organ allocation process,and plays a major role in reduced access to transplantation.For patients with existing barriers to care,such as racial/ethnic minorities,these effects may be even more drastic.Transplant committees must ensure thorough documentation to correctly encapsulate the entirety of a patient’s position and give voice to an already vulnerable population.
基金Supported by The National Natural Science Foundation of China,No.81871080the Key R&D Program of Jining(Major Program),No.2023YXNS004+2 种基金the National Natural Science Foundation of China,No.81401486the Natural Science Foundation of Liaoning Province of China,No.20170540276the Medicine and Health Science Technology Development Program of Shandong Province,No.202003070713.
文摘BACKGROUND Panic disorder(PD)involves emotion dysregulation,but its underlying mechanisms remain poorly understood.Previous research suggests that implicit emotion regulation may play a central role in PD-related emotion dysregulation and symptom maintenance.However,there is a lack of studies exploring the neural mechanisms of implicit emotion regulation in PD using neurophysiological indicators.AIM To study the neural mechanisms of implicit emotion regulation in PD with eventrelated potentials(ERP).METHODS A total of 25 PD patients and 20 healthy controls(HC)underwent clinical evaluations.The study utilized a case-control design with random sampling,selecting participants for the case group from March to December 2018.Participants performed an affect labeling task,using affect labeling as the experimental condition and gender labeling as the control condition.ERP and behavioral data were recorded to compare the late positive potential(LPP)within and between the groups.RESULTS Both PD and HC groups showed longer reaction times and decreased accuracy under the affect labeling.In the HC group,late LPP amplitudes exhibited a dynamic pattern of initial increase followed by decrease.Importantly,a significant group×condition interaction effect was observed.Simple effect analysis revealed a reduction in the differences of late LPP amplitudes between the affect labeling and gender labeling conditions in the PD group compared to the HC group.Furthermore,among PD patients under the affect labeling,the late LPP was negatively correlated with disease severity,symptom frequency,and intensity.CONCLUSION PD patients demonstrate abnormalities in implicit emotion regulation,hampering their ability to mobilize cognitive resources for downregulating negative emotions.The late LPP amplitude in response to affect labeling may serve as a potentially valuable clinical indicator of PD severity.
文摘The halopyrimidine 5-bromo-2′-deoxyuridine(BrdU)is an exogenous marker of DNA synthesis.Since the introduction of monoclonal antibodies against BrdU,an increasing number of methodologies have been used for the immunodetection of this synthesized bromine-tagged base analogue into replicating DNA.BrdU labeling is widely used for identifying neuron precursors and following their fate during the embryonic,perinatal,and adult neurogenesis in a variety of vertebrate species including birds,reptiles,and mammals.Due to BrdU toxicity,its incorporation into replicating DNA presents adverse consequences on the generation,survival,and settled patterns of cells.This may lead to false results and misinterpretation in the identification of proliferative neuroblasts.In this review,I will indicate the detrimental effects of this nucleoside during the development of the central nervous system,as well as the reliability of BrdU labeling to detect proliferating neuroblasts.Moreover,it will show factors influencing BrdU immunodetection and the contribution of this nucleoside to the study of prenatal,perinatal,and adult neurogenesis.Human adult neurogenesis will also be discussed.It is my hope that this review serves as a reference for those researchers who focused on detecting cells that are in the synthetic phase of the cell cycle.
基金financially supported in part by the National Natural Science Fund of China for Distinguished Young Scholars(No.81825023)National Natural Science Foundation of China(No.82003979)Natural Science Foundation of Shanghai(No.23ZR1459100)。
文摘Small peptides have attracted increasing attention for their unique features and diverse biological functions.Achieving rapid separation and accurate quantification,however,remains a challenge because of their low abundance and the co-existence of numerous structural isomers.In this study,we developed a novel approach using isotope chemical labeling for ultrasensitive determination of di/tripeptides in biological samples.We successfully synthesized a novel derivatization reagent,4-(2-(ethoxymethylene)-3-oxobutanamido)-N,N,N-trimethylbenzenaminium iodide(EOTMBA)as well as its deuterium-labeled isotope reagent(d_(3)-EOTMBA).A total of 97 small peptides,including 89 dipeptides and 8 tripeptides,could be completely derivatized in methanol within 1.5h at 60℃.After EOTMBA labeling,analysis of these di/tripeptides were achieved within 22 min by LC-MS/MS analysis.The method demonstrated 86.3%-113%accuracy and the limit of quantification ranged from 0.25 fmol/L to 5 nmol/L.Using this method,we achieved ultrasensitive and accurate quantification of di/tripeptides in 147 plasma,49 urine and 46 bile samples obtained from healthy individuals and patients with biliary tract diseases.The identified differential di/tripeptide biomarker panels showed promising diagnostic performance for patients with biliary tract cancer with area under the receiver operating curve values from 0.870 to 0.996.Furthermore,this method was successfully applied to quantify di/tripeptides in the extract of an animal-derived traditional Chinese medicine,Eupolyphaga sinensis Walker.These findings highlight the possible application of the analytical method in clinics and for the purposes of quality control of traditional Chinese medicines.
基金Supported by The Key Research and Development Program Projects of Shaanxi Province of China,No.S2023-YF-YBSF-0273Natural Science Foundation of Shaanxi Province of China,No.2022JQ-900.
文摘BACKGROUND Global and regional cerebral blood flow(CBF)changes in patients with unilateral internal carotid artery occlusion(ICAO)are unclear when the dual post-labeling delays(PLD)arterial spin labeling(ASL)magnetic resonance imaging(MRI)technique is used.Manual delineation of regions of interest for CBF measurement is time-consuming and laborious.AIM To assess global and regional CBF changes in patients with unilateral ICAO with the ASL-MRI perfusion technique.METHODS Twenty hospitalized patients with ICAO and sex-and age-matched controls were included in the study.Regional CBF was measured by Dr.Brain's ASL software.The present study evaluated differences in global,middle cerebral artery(MCA)territory,anterior cerebral artery territory,and Alberta Stroke Program Early Computed Tomography Score(ASPECTS)regions(including the caudate nucleus,lentiform nucleus,insula ribbon,internal capsule,and M1-M6)and brain lobes(including frontal,parietal,temporal,and insular lobes)between ICAO patients and controls at PLD 1.5 s and PLD 2.5 s.RESULTS When comparing CBF between ICAO patients and controls,the global CBF in ICAO patients was lower at both PLD 1.5 s and PLD 2.5 s;the CBF on the occluded side was lower in 15 brain regions at PLD 1.5 s,and it was lower in 9 brain regions at PLD 2.5 s;the CBF in the contralateral hemisphere was lower in the caudate nucleus and internal capsule at PLD 1.5 s and in M6 at PLD 2.5 s.The global CBF in ICAO patients was lower at PLD 1.5 s than at PLD 2.5 s.The ipsilateral CBF at PLD 1.5 s was lower than that at PLD 2.5 s in 15 regions,whereas the contralateral CBF was lower at PLD 1.5 s than at PLD 2.5 s in 12 regions.The ipsilateral CBF was lower than the contralateral CBF in 15 regions at PLD 1.5 s,and in M6 at PLD 2.5 s.CONCLUSION Unilateral ICAO results in hypoperfusion in the global and MCA territories,especially in the ASPECTS area.Dual PLD settings prove more suitable for accurate CBF quantification in ICAO.
基金supported by National Key R&D Program of China(2021YFA1502803)the National Natural Science Foundation of China(NSFC)(21972066,91745202)+3 种基金NSFC-Royal Society Joint Program(21661130149)L.P.thanks the Royal Society and Newton Fund for a Royal Society-Newton Advanced Fellowshipsupported by the Research Funds for the Frontiers Science Centre for Critical Earth Material Cycling,Nanjing Universitya Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Recent advances in utilizing ^(17)O isotopic labeling methods for solid-state nuclear magnetic resonance(NMR)investigations of metal oxides for lithium-ion batteries have yielded extensive insights into their structural and dynamic details.Herein,we commence with a brief introduction to recent research on lithium-ion battery oxide materials studied using ^(17)O solid-state NMR spectroscopy.Then we delve into a review of ^(17)O isotopic labeling methods for tagging oxygen sites in both the bulk and surfaces of metal oxides.At last,the unresolved problems and the future research directions for advancing the ^(17)O labeling technique are discussed.
文摘The study of the neuron has always been a fundamental aspect when it came to studying mental illnesses such as autism and depression. The protein protocadherin-9 (PCDH9) is an important transmembrane protein in the development of the neuron synapse. Hence, research on its protein interactome is key to understanding its functionality and specific properties. A newly discovered biotin ligase, TurboID, is a proximity labeler that is designed to be able to label and observe transmembrane proteins, something that previous methods struggled with. The TurboID method is verified in HEK293T cells and primary cultured mouse cortical neurons. Results have proven the validity of the TurboID method in observing PCDH9-interacting proteins.
基金supported by the National Natural Science Foundation of China,Nos.32100899(to KZL),31830035(to FQX),31771156(to FQX),21921004(to FQX)the National Science and Technology Innovation 2030,No.2021ZD0201003(to FQX)+2 种基金the Key-Area Research and Development Program of Guangdong Province,No.2018B030331001(to FQX)the Strategic Priority Research Program of the Chinese Academy of Sciences,No.XDB32030200(to FQX)the Shenzhen Key Laboratory of Viral Vectors for Biomedicine,No.ZDSYS20200811142401005(to FQX)。
文摘Analyzing the structure and function of the brain's neural network is critical for identifying the working principles of the brain and the mechanisms of brain diseases.Recombinant rabies viral vectors allow for the retrograde labeling of projection neurons and cell type-specific trans-monosynaptic tracing,making these vectors powerful candidates for the dissection of synaptic inputs.Although several attenuated rabies viral vectors have been developed,their application in studies of functional networks is hindered by the long preparation cycle and low yield of these vectors.To overcome these limitations,we developed an improved production system for the rapid rescue and preparation of a high-titer CVS-N2c-ΔG virus.Our results showed that the new CVS-N2c-ΔG-based toolkit performed remarkably:(1)N2cG-coated CVS-N2c-ΔG allowed for efficient retrograde access to projection neurons that were unaddressed by rAAV9-Retro,and the efficiency was six times higher than that of rAAV9-Retro;(2)the trans-monosynaptic efficiency of oG-mediated CVS-N2c-ΔG was 2–3 times higher than that of oG-mediated SAD-B19-ΔG;(3)CVS-N2c-ΔG could delivery modified genes for neural activity monitoring,and the time window during which this was maintained was 3 weeks;and(4)CVS-N2c-ΔG could express sufficient recombinases for efficient transgene recombination.These findings demonstrate that new CVS-N2c-ΔG-based toolkit may serve as a versatile tool for structural and functional studies of neural circuits.
基金the National Key R&D Program of China(2022YFB3402100)the National Science Fund for Distinguished Young Scholars of China(52025056)+4 种基金the National Natural Science Foundation of China(52305129)the China Postdoctoral Science Foundation(2023M732789)the China Postdoctoral Innovative Talents Support Program(BX20230290)the Open Foundation of Hunan Provincial Key Laboratory of Health Maintenance for Mechanical Equipment(2022JXKF JJ01)the Fundamental Research Funds for Central Universities。
文摘The success of deep transfer learning in fault diagnosis is attributed to the collection of high-quality labeled data from the source domain.However,in engineering scenarios,achieving such high-quality label annotation is difficult and expensive.The incorrect label annotation produces two negative effects:1)the complex decision boundary of diagnosis models lowers the generalization performance on the target domain,and2)the distribution of target domain samples becomes misaligned with the false-labeled samples.To overcome these negative effects,this article proposes a solution called the label recovery and trajectory designable network(LRTDN).LRTDN consists of three parts.First,a residual network with dual classifiers is to learn features from cross-domain samples.Second,an annotation check module is constructed to generate a label anomaly indicator that could modify the abnormal labels of false-labeled samples in the source domain.With the training of relabeled samples,the complexity of diagnosis model is reduced via semi-supervised learning.Third,the adaptation trajectories are designed for sample distributions across domains.This ensures that the target domain samples are only adapted with the pure-labeled samples.The LRTDN is verified by two case studies,in which the diagnosis knowledge of bearings is transferred across different working conditions as well as different yet related machines.The results show that LRTDN offers a high diagnosis accuracy even in the presence of incorrect annotation.
文摘Background In this work,we focus on the label layout problem:specifying the positions of overlaid virtual annotations in Virtual/Augmented Reality scenarios.Methods Designing a layout of labels that does not violate domain-specific design requirements,while at the same time satisfying aesthetic and functional principles of good design,can be a daunting task even for skilled visual designers.Presenting the annotations in 3D object space instead of projection space,allows for the preservation of spatial and depth cues.This results in stable layouts in dynamic environments,since the annotations are anchored in 3D space.Results In this paper we make two major contributions.First,we propose a technique for managing the layout and rendering of annotations in Virtual/Augmented Reality scenarios by manipulating the annotations directly in 3D space.For this,we make use of Artificial Potential Fields and use 3D geometric constraints to adapt them in 3D space.Second,we introduce PartLabeling:an open source platform in the form of a web application that acts as a much-needed generic framework allowing to easily add labeling algorithms and 3D models.This serves as a catalyst for researchers in this field to make their algorithms and implementations publicly available,as well as ensure research reproducibility.The PartLabeling framework relies on a dataset that we generate as a subset of the original PartNet dataset consisting of models suitable for the label management task.The dataset consists of 10003D models with part annotations.
文摘File labeling techniques have a long history in analyzing the anthological trends in computational linguistics.The situation becomes worse in the case of files downloaded into systems from the Internet.Currently,most users either have to change file names manually or leave a meaningless name of the files,which increases the time to search required files and results in redundancy and duplications of user files.Currently,no significant work is done on automated file labeling during the organization of heterogeneous user files.A few attempts have been made in topic modeling.However,one major drawback of current topic modeling approaches is better results.They rely on specific language types and domain similarity of the data.In this research,machine learning approaches have been employed to analyze and extract the information from heterogeneous corpus.A different file labeling technique has also been used to get the meaningful and`cohesive topic of the files.The results show that the proposed methodology can generate relevant and context-sensitive names for heterogeneous data files and provide additional insight into automated file labeling in operating systems.
基金the Ministry of Science and Technology of Taiwan,Grant Number MOST 110-2221-E-507-003.
文摘Hiding secret data in digital images is one of the major researchfields in information security.Recently,reversible data hiding in encrypted images has attracted extensive attention due to the emergence of cloud services.This paper proposes a novel reversible data hiding method in encrypted images based on an optimal multi-threshold block labeling technique(OMTBL-RDHEI).In our scheme,the content owner encrypts the cover image with block permutation,pixel permutation,and stream cipher,which preserve the in-block correlation of pixel values.After uploading to the cloud service,the data hider applies the prediction error rearrangement(PER),the optimal threshold selection(OTS),and the multi-threshold labeling(MTL)methods to obtain a compressed version of the encrypted image and embed secret data into the vacated room.The receiver can extract the secret,restore the cover image,or do both according to his/her granted authority.The proposed MTL labels blocks of the encrypted image with a list of threshold values which is optimized with OTS based on the features of the current image.Experimental results show that labeling image blocks with the optimized threshold list can efficiently enlarge the amount of vacated room and thus improve the embedding capacity of an encrypted cover image.Security level of the proposed scheme is analyzed and the embedding capacity is compared with state-of-the-art schemes.Both are concluded with satisfactory performance.
基金supported in part by the National Key R&D Program of China (2023YFA1011601)the Major Key Project of PCL, China (PCL2023AS7-1)+3 种基金in part by the National Natural Science Foundation of China (U21A20478, 62106224, 92267203)in part by the Science and Technology Major Project of Guangzhou (202007030006)in part by the Major Key Project of PCL (PCL2021A09)in part by the Guangzhou Science and Technology Plan Project (2024A04J3749)。
文摘Multi-label classification is a challenging problem that has attracted significant attention from researchers, particularly in the domain of image and text attribute annotation. However, multi-label datasets are prone to serious intra-class and inter-class imbalance problems, which can significantly degrade the classification performance. To address the above issues, we propose the multi-label weighted broad learning system(MLW-BLS) from the perspective of label imbalance weighting and label correlation mining. Further, we propose the multi-label adaptive weighted broad learning system(MLAW-BLS) to adaptively adjust the specific weights and values of labels of MLW-BLS and construct an efficient imbalanced classifier set. Extensive experiments are conducted on various datasets to evaluate the effectiveness of the proposed model, and the results demonstrate its superiority over other advanced approaches.
文摘The Nutri-Score is a 5-color front-of-pack nutrition label designed to provide consumers with an easily understandable guideline to the healthiness of food products.The impact that the Nutri-Score may have on consumers'choices is unclear since different experimental paradigms have found vastly different effect sizes.In the present study,we have investigated how student participants change a hypothetical personal 1-daydietary plan after a learning phase during which they learn about the Nutri-Scores of the available food items.Participants were instructed to compose a healthy diet plan in order that the question of whether the NutriScore would improve their ability to compose a healthy dietary plan could be investigated,independent of the question of whether they would apply this knowledge in their ordinary lives.We found a substantial(Cohen's d=0.86)positive impact on nutritional quality(as measured by the Nutrient Profiling System score of the Food Standards Agency)and a medium-sized(Cohen's d=0.43)reduction of energy content.Energy content reduction was larger for participants who had initially composed plans with higher energy content.The results suggest that the Nutri-Score has the potential to guide consumers to healthier food choices.It remains unclear,however,whether this potential will be reflected in real-life dietary choices.
文摘Interpreted the latest cosmetic labeling requirements one by one from the basic principles on labels,content, positions, preceded terms and so on;analyzed the relevant cases, so as to help cosmetic manufacturers and operation enterprises to deeply understand the latest requirements on cosmetics labeling after the promulgation of the new regulations.
文摘Recently,weak supervision has received growing attention in the field of salient object detection due to the convenience of labelling.However,there is a large performance gap between weakly supervised and fully supervised salient object detectors because the scribble annotation can only provide very limited foreground/background information.Therefore,an intuitive idea is to infer annotations that cover more complete object and background regions for training.To this end,a label inference strategy is proposed based on the assumption that pixels with similar colours and close positions should have consistent labels.Specifically,k-means clustering algorithm was first performed on both colours and coordinates of original annotations,and then assigned the same labels to points having similar colours with colour cluster centres and near coordinate cluster centres.Next,the same annotations for pixels with similar colours within each kernel neighbourhood was set further.Extensive experiments on six benchmarks demonstrate that our method can significantly improve the performance and achieve the state-of-the-art results.
基金the Natural Science Foundation of China(Grant Numbers 72074014 and 72004012).
文摘Purpose:Many science,technology and innovation(STI)resources are attached with several different labels.To assign automatically the resulting labels to an interested instance,many approaches with good performance on the benchmark datasets have been proposed for multi-label classification task in the literature.Furthermore,several open-source tools implementing these approaches have also been developed.However,the characteristics of real-world multi-label patent and publication datasets are not completely in line with those of benchmark ones.Therefore,the main purpose of this paper is to evaluate comprehensively seven multi-label classification methods on real-world datasets.Research limitations:Three real-world datasets differ in the following aspects:statement,data quality,and purposes.Additionally,open-source tools designed for multi-label classification also have intrinsic differences in their approaches for data processing and feature selection,which in turn impacts the performance of a multi-label classification approach.In the near future,we will enhance experimental precision and reinforce the validity of conclusions by employing more rigorous control over variables through introducing expanded parameter settings.Practical implications:The observed Macro F1 and Micro F1 scores on real-world datasets typically fall short of those achieved on benchmark datasets,underscoring the complexity of real-world multi-label classification tasks.Approaches leveraging deep learning techniques offer promising solutions by accommodating the hierarchical relationships and interdependencies among labels.With ongoing enhancements in deep learning algorithms and large-scale models,it is expected that the efficacy of multi-label classification tasks will be significantly improved,reaching a level of practical utility in the foreseeable future.Originality/value:(1)Seven multi-label classification methods are comprehensively compared on three real-world datasets.(2)The TextCNN and TextRCNN models perform better on small-scale datasets with more complex hierarchical structure of labels and more balanced document-label distribution.(3)The MLkNN method works better on the larger-scale dataset with more unbalanced document-label distribution.
基金supported by the National Outstanding Youth Science Fund Project of National Natural Science Foundation of China[Grant No.52222708]the Natural Science Foundation of Beijing Municipality[Grant No.3212033]。
文摘Battery pack capacity estimation under real-world operating conditions is important for battery performance optimization and health management,contributing to the reliability and longevity of batterypowered systems.However,complex operating conditions,coupling cell-to-cell inconsistency,and limited labeled data pose great challenges to accurate and robust battery pack capacity estimation.To address these issues,this paper proposes a hierarchical data-driven framework aimed at enhancing the training of machine learning models with fewer labeled data.Unlike traditional data-driven methods that lack interpretability,the hierarchical data-driven framework unveils the“mechanism”of the black box inside the data-driven framework by splitting the final estimation target into cell-level and pack-level intermediate targets.A generalized feature matrix is devised without requiring all cell voltages,significantly reducing the computational cost and memory resources.The generated intermediate target labels and the corresponding features are hierarchically employed to enhance the training of two machine learning models,effectively alleviating the difficulty of learning the relationship from all features due to fewer labeled data and addressing the dilemma of requiring extensive labeled data for accurate estimation.Using only 10%of degradation data,the proposed framework outperforms the state-of-the-art battery pack capacity estimation methods,achieving mean absolute percentage errors of 0.608%,0.601%,and 1.128%for three battery packs whose degradation load profiles represent real-world operating conditions.Its high accuracy,adaptability,and robustness indicate the potential in different application scenarios,which is promising for reducing laborious and expensive aging experiments at the pack level and facilitating the development of battery technology.